It is particularly important in the pharmaceutical field to be able to prepare pharmaceutical preparations comprising particles having extremely small dimensions and additionally having a remarkable homogeneity of distribution. These needs are especially important for the pharmaceutical preparations intended for parenteral administration.
Certain active principals also require a coating for their administration. This leads to a double problem of obtaining pharmaceutical forms having as small a diameter as possible, the active principal being coated by a polymer and the whole necessarily being able to be administered to man or to animals. This polymer must also have properties of bio-compatibility and biodegradability.
This general problem has been known by the pharmaceutical industry for a long time. Various descriptions of microparticles have already been proposed, such as, for example, in U.S. Pat. No. 4,330,338. This patent, which does not answer the problem previously mentioned, describes a process for the preparation of polymer microspheres and their subsequent addition to pharmaceutical active principals during the preparation, for example, of tablets. According to this patent, polymer microspheres are prepared by dissolving the water-insoluble polymer in a solvent, which is more volatile than water, and this solution is then emulsified in an aqueous phase, optionally in the presence of an emulsifying agent, and the solvent is finally evaporated. The microspheres obtained have a diameter of between 0.1 to and 20 microns. They are used for coating pharmaceutical active principals. It is specified in this patent that to obtain the desired amount of coating when the polymer is insoluble in water, it is necessary to add to the emulsion an agent such as a water-soluble polymer such as, for example, methylcellulose or polyvinylpyrrolidone. These agents which favor coating are chosen from compounds which are soluble in water and acceptable for ingestion. Unfortunately, most of them are not acceptable for administration by the parenteral route. This patent never describes the coating of a pharmaceutical active principal in the form of microspheres and therefore does not resolve the problem previously mentioned.
Microspheres of active principals coated with a copolymer based on polylactic acid are also described in the EP Patent No. 269,921. These microspheres have an average diameter of between 0.1 and 10 microns. They are obtained by dissolving the polymer and the active principal to be coated in a water-immiscible solvent, followed by emulsion of the above solution in an aqueous solution containing an emulsifier and applying ultrasonic waves. The emulsifier is chosen from polyvinyl alcohol, polyvinylpyrrolidone and carboxymethylcellulose. The only emulsifier exemplified is polyvinyl alcohol. It is impossible for administration to man by the injection route to keep track of such a compound. Moreover, the use of this ultrasonification process results in an unacceptably high presence of heavy metals.
According to GB Patent No. 2,077,693, microspheres having a diameter of less than 150 .mu.m and even of between 5 and 25 .mu.m, which are obtained by emulsion of an organic solution of the biodegradable and biocompatible polymer and of an aqueous solution of a fatty acid salt, are also described. The fatty acid salts are not biocompatible and this patent excludes the sole presence of emulsifier, such as gelatin.